The effect of a locally tailored intervention on the uptake of preconception care in the Netherlands: a stepped-wedge cluster randomized trial (APROPOS-II study).

BACKGROUND: The preconception period provides a window of opportunity for interventions aiming to reduce unhealthy lifestyle behaviours and their negative effect on pregnancy outcomes. This study aimed to assess the effectiveness of a locally tailored preconception care (PCC) intervention in a hybrid-II effectiveness implementation design. METHODS: A stepped-wedge cluster randomized controlled trial was performed in four Dutch municipalities. The intervention contained a social marketing strategy aiming to improve the uptake (prospective parents) and the provision (healthcare providers) of PCC. Prospective parents participated by administering a questionnaire in early pregnancy recalling their preconceptional behaviours. Experiences of healthcare providers were also evaluated through questionnaires. The composite primary outcome was adherence to at least three out of four preconceptional lifestyle recommendations (early initiation of folic acid supplements, healthy nutrition, no smoking or alcohol use). Secondary outcomes were preconceptional lifestyle behaviour change, (online) reach of the intervention and improved knowledge among healthcare providers. RESULTS: A total of 850 women and 154 men participated in the control phase and 213 women and 39 men in the intervention phase. The composite primary outcome significantly improved among women participating in the municipality where the reach of the intervention was highest (Relative Risk (RR) 1.57 (95% Confidence Interval (CI) 1.11-2.22). Among women, vegetable intake had significantly improved in the intervention phase (RR 1.82 (95%CI 1.14-2.91)). The aimed online reach- and engagement rate of the intervention was achieved most of the time. Also, after the intervention, more healthcare providers were aware of PCC-risk factors (54.5% vs. 47.7%; p = 0.040) and more healthcare providers considered it easier to start a conversation about PCC (75.0% vs. 47.9%; p = 0.030). CONCLUSION: The intervention showed some tentative positive effects on lifestyle behaviours among prospective parents. Primarily on vegetable intake and the knowledge and competence of healthcare providers. The results of this study contribute to the evidence regarding successfully implementing PCC-interventions to optimize the health of prospective parents and future generations. TRIAL REGISTRATION: Dutch Trial Register: NL7784 (Registered 06/06/2019).

Incidence and predictors of thoracic aortic damage in biopsy-proven giant cell arteritis.

Objective: To describe the frequency and predisposing factors of aortic structural disease among patients with biopsy-proven giant cell arteritis (GCA).Method: A retrospective review identified all patients with biopsy-proven GCA from 1998 to 2013 with aortic imaging. Kaplan-Meier methods were used to estimate cumulative incidence and Cox models were used to examine potential predictors of development of aneurysm/dilatation of the thoracic aorta.Results: The cohort included 114 patients with aortic imaging performed within a median time of 1.8 months from GCA diagnosis. Fifty-seven patients (50%) had at least one additional follow-up imaging study. At the first imaging study, 8% had evidence of aneurysm/dilatation and 25% thickening of the thoracic aorta. Excluding prevalent cases, the cumulative incidence for aneurysm/dilatation of the thoracic aorta during follow-up was 0% at both 1 year and 2 years but increased to 10% at 5 years. The sole predictor for development of thoracic aortic aneurysm/dilatation was current smoking (hazard ratio 28.8, 95% confidence interval 1.62, 511.4; p = 0.02).Conclusion: Thoracic aortic aneurysm/dilatation was seen in 8% of patients at baseline. Among patients without aortic disease, the cumulative incidence of aortic disease was 10% at 5 years after diagnosis. Current smokers were at an increased risk for developing thoracic aortic damage. Surveillance for aortic damage should be pursued in patients with GCA, particularly those with a smoking history.

Immunoglobulin A vasculitis associated with inflammatory bowel disease: a retrospective cohort study.

Objective: To describe the baseline characteristics and outcome of a series of patients with inflammatory bowel disease (IBD) and immunoglobulin A vasculitis (IgAV). Method: Patients with biopsy-proven IgAV with IBD were identified retrospectively. Data were abstracted from direct medical chart review. Each IBD-IgAV case was matched to two controls with IgAV but without IBD. Results: Nine patients were identified (seven Crohn's disease, two ulcerative colitis). Mean length of time between IBD diagnosis and IgAV onset was 17.3 ± 19.9 years. For patients on biologic treatment for IBD, mean length of time between biologic initiation and IgAV onset was 3.3 ± 3.8 years. Active IBD at IgAV onset was present in 56%. Tumour necrosis factor inhibitors (TNFi) were used for IBD in 89%. At IgAV onset, six patients were on treatment with TNFi; one subsequently discontinued, two switched to another TNFi, and three continued. At the last follow-up, three of five patients who remained on TNFi had full resolution of IgAV despite ongoing TNFi use. No differences were seen between cases with IBD IgAV and matched non-IBD-IgAV controls regarding development of end-stage renal disease, resolution of haematuria or proteinuria, and time to complete IgAV response. Conclusion: Baseline characteristics and outcomes of patients with IBD-IgAV are similar to those with IgAV without IBD. Development of IgAV is not limited to patients with clinically active IBD. Whether TNFi use is related to the pathogenesis of IgAV in some patients with IBD remains unclear. Further research into pathophysiological connections between IBD and IgAV is needed.

Improving recognition of potential tissue donors: a quality improvement project by a hospitalist in training in The Hague, The Netherlands.

The number of tissue donations decreased in The Netherlands over recent years. The aim of this project was to determine the number of missed tissue donors in the Haaglanden Medical Centre and to develop a strategy to improve the number of tissue donors. We retrospectively analyzed patient files of all deceased patients in 2014 for their potential as tissue donors. Our objectives were to determine the number of missed tissue donors and the percentage of correctly identified tissue donors among all physicians and hospitalists in training. In addition, a clinical audit and three focus group interviews were used to determine the level of knowledge about and adherence to local and national protocols. The findings enabled us to suggest national and local improvements to reduce the percentage of missed tissue donors. The number of missed tissue donors was 94 (17.2%) of 548 deceased patients in 2014. The percentage of correctly identified tissue donors was 65.7% among all physicians (Cohen's Kappa coefficient 0.557, p ≤ 0.001) and 57.1% among hospitalists in training (Cohen's Kappa coefficient 0.492, p ≤ 0.001). In 31 patients (32.4%), the reported contra-indication by physicians was not a contra-indication for tissue donation in The Netherlands. There was no statistical difference in correct identification between physicians and hospitalists in training (p = 0.321, Mann-Whitney). The most effective actions to increase the number of tissue donations include to better inform physicians about contra-indications and help them in the recognition of a tissue donor.

Parental perspectives on the awareness and delivery of preconception care.

BACKGROUND: The attention for Preconception Care (PCC) has grown substantially in recent years, yet the implementation of PCC appears challenging as uptake rates remain low. The objective of this study was to assess parental perspectives on how PCC should be provided. METHODS: Recruitment of participants took place among couples who received antenatal care at a Dutch community midwifery practice. Between June and September 2014, five focus group sessions were held with 29 women and one focus group session with 5 men. Thematic analysis was conducted using NVivo 10 software. RESULTS: Participants were generally unfamiliar with the concept of PCC. It was proposed to raise awareness by means of a promotional campaign, stipulating that PCC is suited for every couple with a (future) child wish. Suggestions were made to display marketing materials in both formal and informal (local community) settings. Addressing existing social networks and raising social dialogue was expected to be most efficient. It was recommended to make PCC more accessible by offering multiple forms and to involve male partners. Opportunistic offering PCC by healthcare providers was considered more acceptable when the subject was deliberately raised, for example while discussing contraceptives, lifestyle risks or drug prescriptions. GP's or midwifes were regarded the most suitable PCC providers, however provider characteristics such as experience, empathy and communication skills were considered more important. CONCLUSIONS: This study showed that from the parental perspective it is recommended to address every couple with a (future) child wish by means of enlarging the awareness and accessibility of PCC. In order to enlarge the awareness, it is recommended to address social networks, to raise the social dialogue and to conduct promotional campaigns regarding PCC. In order to improve the accessibility of PCC, it was suggested to simultaneously offer multiple forms: group sessions, individual consultations, walk-in-hours and online sessions, and to involve male partners.

Cumulative changes in weight but not fluid volume balances reflect fluid accumulation in ICU patients.

BACKGROUND: The cumulative fluid balance of critically ill patients seems to be an outcome-relevant variable. However, there are no validated data for their reliability calculated for longer (> 5 days) periods of time. METHODS: All ICU patients ≥ 18 years, with an ICU stay ≥ 5 days and a body weight ≤ 195 kg were evaluated from 1 January 2013 to 31 December 2013. Daily standardized weighing was performed using bed-integrated scales simultaneously with the daily 24-h fluid balance. Simultaneously, a fluid balance without and with insensible perspiration (10 ml/kg/day) was calculated for each 24 h. Primary endpoint: difference between cumulative fluid balance and body weight changes at the day of transfer to the normal ward or the day of death in the ICU, respectively, in each patient. All data are presented as medians with interquartile ranges (IQR) with 25 and 75 percentiles (IQR/25/75) unless otherwise noted. RESULTS: One hundred and six critically ill patients were evaluated; 82 survivors and 24 nonsurvivors. Cumulative 24-h fluid balances rose continuously while body weight decreased over time. Correction of cumulative fluid balances for insensible perspiration (10 ml/kg/day) also did not match with body weight changes. Only survivors had a significant loss in body weight -1.8 (27.5/-6.1/1.0) kg. CONCLUSIONS: Assuming that changes in body weight reflect changes in whole body water content cumulative daily fluid volume balances without or with correction for insensible water loss are not useful for estimating cumulative fluid balance of ICU patients. Survivors but not nonsurvivors had a significant loss of weight over time.

Healthcare providers' views on the delivery of preconception care in a local community setting in the Netherlands.

BACKGROUND: The attention for preconception care (PCC) has grown substantially in recent years, yet PCC is far from routine in daily practice. One of the major challenges for the implementation of PCC is to identify how it can best be organized and provided within the primary care setting. The aim of this study was to identify bottlenecks and solutions for the delivery of PCC from a healthcare providers' perspective in a local community setting in the Netherlands. METHODS: Health professionals within the region of Zeist, the Netherlands, were invited for a meeting on the local implementation of PCC. Five parallel group sessions were held with 30 participants from different disciplines. The sessions were moderated based on the Nominal Group Technique, in which bottlenecks (step 1) and solutions (step 2) for the delivery of PCC were gathered, categorized and prioritized by the participants. RESULTS: Participants expressed that the provision of PCC is challenging due to lack of awareness, the absence of a costing structure and unclear allocation of responsibilities. The most pragmatic approach considered was to make interdisciplinary arrangements within the local primary care setting. Participants recommended to 1) settle a costing structure by means of third party reimbursement, 2) improve collaboration by means of a local cooperation network and an adequate referral system, 3) invest in education, tools and logistics and 4) increase uptake rates by the routine opportunistic offer of PCC and promotional campaigns. CONCLUSIONS: From a provider's perspective a tailored approach is advocated in which interdisciplinary arrangements for collaboration and referral are set up within the local primary care setting.

Review of 103 Swedish Healthcare Quality Registries.

BACKGROUND AND OBJECTIVES: In the past two decades, an increasing number of nationwide, Swedish Healthcare Quality Registries (QRs) focusing on specific disorders have been initiated, mostly by physicians. Here, we describe the purpose, organization, variables, coverage and completeness of 103 Swedish QRs. METHODS: From March to September 2013, we examined the 2012 applications of 103 QRs to the Swedish Association of Local Authorities and Regions (SALAR) and also studied the annual reports from the same QRs. After initial data abstraction, the coordinator of each QR was contacted at least twice between June and October 2013 and asked to confirm the accuracy of the data retrieved from the applications and reports. RESULTS: About 60% of the QRs covered ≥80% of their target population (completeness). Data recorded in Swedish QRs include aspects of disease management (diagnosis, clinical characteristics, treatment and lead times). In addition, some QRs retrieve data on self-reported quality of life (EQ5D, SF-36 and disease-specific measures), lifestyle (smoking) and general health status (World Health Organization performance status, body mass index and blood pressure). CONCLUSION: Detailed clinical data available in Swedish QRs complement information from government-administered registries and provide an important source not only for assessment and development of quality of care but also for research.

Androgen levels in women with various forms of ovarian dysfunction: associations with cardiometabolic features.

STUDY QUESTION: Are differences in androgen levels among women with various forms of ovarian dysfunction associated with cardiometabolic abnormalities? SUMMARY ANSWER: Androgen levels differed substantially between women with and without ovarian dysfunction, and increased androgen levels were associated with impaired cardiometabolic features in all women irrespective of their clinical condition. WHAT IS KNOWN ALREADY: Sex steroid hormones play important roles in the development of cardiovascular diseases (CVD). Extremes of low as well as high androgen levels have been associated with increased CVD risk in both men and women. STUDY DESIGN, SIZE, DURATION: This cross-sectional study included 680 women with polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), natural post-menopausal women (NM), or regular menstrual cycles (RC) (170 women per group). PARTICIPANTS/MATERIALS, SETTING, METHODS: Measurements of serum testosterone, androstenedione and dehydroepiandrosterone sulfate were performed using liquid chromatography-tandem mass spectrometry. Assessments were taken of body mass index (BMI), blood pressure, lipid profiles, glucose, insulin and SHBG, and the bioactive fraction of circulating testosterone was calculated using the free androgen index (FAI). MAIN RESULTS AND THE ROLE OF CHANCE: PCOS women were hyperandrogenic [median FAI = 4.9 (IQR 3.6-7.4)], and POI women were hypoandrogenic [FAI = 1.2 (0.8-1.7)], compared with RC women [FAI = 1.7 (1.1-2.8)], after adjustment for age, ethnicity, smoking and BMI (P < 0.001). After adjustment for age, there were no significant differences in androgens between POI and NM (P = 0.15) women and between NM and RC (P = 0.27) women, the latter indicating that chronological aging rather than ovarian aging influences the differences between pre- and post-menopausal women. A high FAI was associated with elevated triglycerides (ß log FAI for PCOS: 0.45, P < 0.001, POI: 0.25, P < 0.001, NM: 0.20, P = 0.002), insulin (ß log FAI for PCOS: 0.77, POI: 0.44, NM: 0.40, all P < 0.001), HOMA-IR (ß log FAI for PCOS: 0.82, POI: 0.46, NM: 0.47, all P < 0.001) and mean arterial pressure (ß log FAI for PCOS: 0.05, P = 0.002, POI: 0.07, P < 0.001, NM: 0.04, P = 0.04) in all women; with increased glucose (ß log FAI for PCOS: 0.05, P = 0.003, NM: 0.07, P < 0.001) and decreased high-density lipoprotein (ß log FAI for PCOS: -0.23, P < 0.001, NM: -0.09, P = 0.03) in PCOS and NM women; and with increased low-density lipoprotein (ß log FAI for POI: 0.083, P = 0.041) in POI women. Adjustment for BMI attenuated the observed associations. Associations between FAI and cardiometabolic features were the strongest in PCOS women, even after adjustment for BMI. LIMITATIONS, REASONS FOR CAUTION: Associations between androgen levels and cardiometabolic features were assessed in PCOS, POI and NM women only, due to a lack of available data in RC women. Due to the cross-sectional design of the current study, the potential associations between androgen levels and actual future cardiovascular events could not be assessed. WIDER IMPLICATIONS OF THE FINDINGS: This study affirms the potent effect of androgens on cardiometabolic features, indicating that androgens should indeed be regarded as important denominators of women's health. Future research regarding the role of androgens in the development of CVD and potential modulatory effects of BMI is required. STUDY FUNDING/COMPETING INTERESTS: N.M.P.D. is supported by the Dutch Heart Foundation (grant number 2013T083). L.J. and O.H.F. work in ErasmusAGE, a center for aging research across the life course, funded by Nestlé Nutrition (Nestec Ltd), Metagenics Inc. and AXA. M.K. is supported by the AXA Research Fund. Nestlé Nutrition (Nestec Ltd), Metagenics Inc. and AXA had no role in the design and conduct of the study; the collection, management, analysis and interpretation of the data; or the preparation, review or approval of the manuscript. J.S.E.L. has received fees and grant support from the following companies (in alphabetical order): Ferring, Merck-Serono, Merck Sharpe & Dome, Organon, Schering Plough and Serono. In the last 5 years, B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order); Actavis, COGI, Euroscreen, Ferring, Finox, Genovum, Gedeon-Richter, Merck-Serono, OvaScience, Pantharei Bioscience, PregLem, Roche, Uteron and Watson laboratories. With regard to potential conflicts of interest, there is nothing further to disclose.

Human fetal growth is constrained below optimal for perinatal survival.

OBJECTIVE: The use of fetal growth charts assumes that the optimal size at birth is at the 50(th) birth-weight centile, but interaction between maternal constraints on fetal growth and the risks associated with small and large fetal size at birth may indicate that this assumption is not valid for perinatal mortality rates. The objective of this study was to investigate the distribution and timing (antenatal, intrapartum or neonatal) of perinatal mortality and morbidity in relation to birth weight and gestational age at delivery. METHODS: Data from over 1 million births occurring at 28-43 weeks' gestation from singleton pregnancies without congenital abnormalities in the period from 2002 to 2008 were collected from The Netherlands Perinatal Registry. The distribution of perinatal mortality according to birth-weight centile and gestational age at delivery was studied. RESULTS: In the 1 170 534 pregnancies studied, there were 5075 (0.43%) perinatal deaths. The highest perinatal mortality occurred in those with a birth weight below the 2.3(rd) centile (25.4/1000 births) and the lowest mortality was in those with birth weights between the 80(th) and 84(th) centiles (2.4/1000 births), according to routinely used growth charts. Antepartum deaths were lowest in those with birth weight between the 90(th) and 95(th) centiles. Data were almost identical when the analysis was restricted to infants born at ≥ 37 weeks' gestation. CONCLUSION: From an immediate survival perspective, optimal fetal growth requires a birth weight between the 80(th) and 84(th) centiles for the population. Median birth weight in the population is, by definition, substantially lower than these centiles, implying that the majority of fetuses exhibit some form of maternal constraint on growth. This finding is consistent with adaptations that have evolved in humans in conjunction with a large head and bipedalism, to reduce the risk of obstructed delivery. These data also fit remarkably well with those on long-term adult cardiovascular and metabolic health risks, which are lowest in cases with a birth weight around the 90(th) centile.

Detection of fetal chromosomal anomalies: does nuchal translucency measurement have added value in the era of non-invasive prenatal testing?

OBJECTIVES: The objective of this study is to determine what percentage of fetal chromosomal anomalies remains undetected when first trimester combined testing is replaced by non-invasive prenatal testing for trisomies 13, 18, and 21. We focused on the added clinical value of nuchal translucency (NT) measurement. METHODS: Data on fetal karyotype, ultrasound findings, and pregnancy outcome of all pregnancies with an NT measurement ≥3.5 mm were retrospectively collected from a cohort of 25,057 singleton pregnancies in which first trimester combined testing was performed. RESULTS: Two hundred twenty-five fetuses (0.9 %) had an NT ≥3.5 mm. In 24 of these pregnancies, a chromosomal anomaly other than trisomy 13, 18, or 21 was detected. Eleven resulted in fetal demise, and ten showed fetal ultrasound anomalies. In three fetuses with normal ultrasound findings, a chromosomal anomaly was detected, of which one was a triple X. CONCLUSIONS: In three out of 25,057 pregnancies (0.01%), non-invasive prenatal testing and fetal ultrasound would have missed a chromosomal anomaly that would have been identified by NT measurement. © 2015 John Wiley & Sons, Ltd.

Preconception predictors of gestational diabetes: a multicentre prospective cohort study on the predominant complication of pregnancy in polycystic ovary syndrome.

STUDY QUESTION: Can we develop an adequate preconception prediction model to identify those women with polycystic ovary syndrome (PCOS) who have an increased risk of developing gestational diabetes mellitus (GDM) during subsequent pregnancy? STUDY ANSWER: The risk of developing GDM in women with PCOS can be adequately predicted prior to conception by a prediction model. WHAT IS KNOWN ALREADY: Women with PCOS are at increased risk of pregnancy complications, especially GDM. GDM has serious short-term and long-term effects on mother and baby. STUDY DESIGN, SIZE, DURATION: This study is a part of a multicentre prospective cohort study, which was conducted between April 2008 and April 2012. A total of 326 women with PCOS were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with PCOS and a wish to conceive were included prior to conception and followed until 6 weeks after delivery. Maternal, neonatal and birth complications were reported. A multivariate model was developed to predict the most common pregnancy complication, GDM, by using univariate and multivariate logistic regression of preconception patient characteristics. The area under the curve (AUC) of the receiver-operating characteristic was used to test the performance of the model. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 189 women (58%) achieved an ongoing pregnancy (8% multiples) and delivered a live-born neonate. One or two maternal complications occurred in 62 (33%) pregnant women, mainly GDM (n = 41; 22%) and pregnancy-induced hypertension (n = 14; 7%). In children, one or two complications were observed in 49 (26%) of 206 children born, e.g. premature delivery (n = 23; 12%) and small for gestational age (n = 15; 8%). The preconception prediction model for GDM performed well (AUC 0.87, 95% CI 0.81-0.93). First-degree relatives with type 2 diabetes mellitus, serum levels of fasting glucose, fasting insulin, androstenedione and sex hormone-binding globulin before conception were identified as predictors. LIMITATIONS, REASONS FOR CAUTIONS: The prediction model has not yet been externally validated in another group of patients. Also, there were missing data for some of the determinants, which were accounted for by multiple imputation. WIDER IMPLICATIONS OF THE FINDINGS: Women with PCOS who achieve a pregnancy have an increased risk of GDM. The prediction model can be used to identify women particularly at risk for GDM who should be monitored closely to enable preventative measures that may reduce the risk of developing GDM and its adverse consequences. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for the study. M.A.W., S.M.V.V., A.J.G., A.F. and M.P.H.K. have nothing to disclose. C.B.L has received fees and grant support from the following companies (in alphabetic order): Auxogen, European Society of Human Reproduction and Embryology and MSD. J.S.E.L. has received fees and grant support from the following companies (in alphabetic order): Ferring, Gennovum, Merck-Serono, MSD, Organon, Schering Plough, Sharp & Dome and Serono. M.J.C. has received grant support from the following companies (in alphabetic order): Illumina and MSD. B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order): Ferring, Ova-Science, PregLem SA, Roche and Watson Laboratories. TRIAL REGISTRATION NUMBER: NCT00821379 [Clinicaltrials.gov].

[Information on early detection of colorectal cancer: development of an information module for the women's health portal of the Federal Center for Health Education (BZgA)]. / Informationen zur Darmkrebsfrüherkennung : Aufbau eines Themenmoduls für das Frauengesundheitsportal der Bundeszentrale für gesundheitliche Aufklärung (BZgA).

Colorectal cancer is the second most prevalent cancer in Germany. The governmental program for early detection of colorectal cancer intends to increase the chances of recovery by identifying colorectal cancer in an early, more treatable stage. Citizens need quality-assured, balanced, and target-group-specific information to be able to make an informed decision. On the basis of the current state of research, of extensive studies, and of expert and user interviews, the Federal Center for Health Education (BZgA) developed an information module on"early detection of colorectal cancer" for the women's health portal of the BZgA. The information module contains information on colorectal cancer, on the governmental program for early detection, as well as on the program's benefits and risks. The information offered is intended to be up to date and is approved by experts. The BZgA approves the quality of this information using methods of process and outcome evaluation.

Postpartum development of metabolic dysfunction-associated steatotic liver disease in a lean mouse model of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is associated with increased postpartum risk for metabolic dysfunction-associated steatotic liver disease (MASLD). GDM-related MASLD predisposes to advanced liver disease, necessitating a better understanding of its development in GDM. This preclinical study evaluated the MASLD development in a lean GDM mouse model with impaired insulin secretion capacity. Lean GDM was induced by short-term 60% high-fat diet and low-dose streptozotocin injections (60 mg/kg for 3 days) before mating in C57BL/6N mice. The control dams received only high-fat diet or low-fat diet. Glucose homeostasis was assessed during pregnancy and postpartum, whereas MASLD was assessed on postpartum day 30 (PP30). GDM dams exhibited a transient hyperglycemic phenotype during pregnancy, with hyperglycaemia reappearing after lactation. Lower insulin levels and impaired glucose-induced insulin response were observed in GDM mice during pregnancy and postpartum. At PP30, GDM dams displayed higher hepatic triglyceride content compared controls, along with increased MAS (MASLD) activity scores, indicating lipid accumulation, inflammation, and cell turnover indices. Additionally, at PP30, GDM dams showed elevated plasma liver injury markers. Given the absence of obesity in this double-hit GDM model, the results clearly indicate that impaired insulin secretion driven pregnancy hyperglycaemia has a distinct contribution to the development of postpartum MASLD.

Evaluation of antenatal umbilical coiling index at 16-21 weeks of gestation as a predictor of trisomy 21 and other chromosomal defects.

OBJECTIVES: To determine whether there is an association between sonographically assessed hyper- or hypocoiling of the umbilical cord and the presence of trisomy 21, to provide reference values for the antenatal umbilical coiling index (aUCI) at a gestational age of 16-21 weeks and to determine whether these measurements are reliable and reproducible. METHODS: This was a prospective study of 737 pregnancies in which the aUCI was measured between 16 and 21 weeks of gestation by ultrasound at the time of amniocentesis. The aUCI was calculated as the reciprocal value of the mean length of one complete coil in centimeters. We created reference curves and studied the relationship with trisomy 21 and other chromosomal defects. In 30 pregnancies we studied the intra- and interobserver variation in measurements using Bland-Altman plots with associated 95% limits of agreement and intraclass correlation coefficients. RESULTS: aUCI was found to be non-linearly related to gestational age at 16-21 weeks and reference curves were created for the mean aUCI and the 2.3(rd) , 10(th) , 90(th) and 97.7(th) percentiles. There was no significant difference in aUCI values between the reference group (n = 714) and cases with trisomy 21 (n = 16) or other aneuploidies (n = 7) (one-way ANOVA, P = 0.716). There was good intra- and interobserver agreement in aUCI measurements. CONCLUSIONS: The aUCI can be measured reliably and varies according to gestational age at 16-21 weeks. The aUCI was not significantly associated with trisomy 21 or other chromosomal defects.

Towards an integrated community approach of overweight prevention: the experiences of practitioners and policymakers.

BACKGROUND: Fighting overweight effectively asks for a community-based coherent integrated approach. The first step in improving the local prevention of overweight is to retrieve practice-based information on the interventions used and the experiences of practitioners. OBJECTIVES: A variety of practitioners and policymakers in three different cities in The Netherlands were interviewed to investigate: what kind of interventions are used in practice today? What is helpful and what does not to implement these interventions? What is needed? How is the collaboration between the parties involved? METHODS: Three observers classified all statements systematically according to the four categories from the implementation model by Fleuren M, Wiefferink K, Paulussen T (Determinants of innovation within health care organizations: literature review and Delphi study. Int J Qual Health Care 2004; 16: 107-123). RESULTS: In Nijmegen, 29 interventions for the prevention or treatment of overweight were identified for the target group youth and 22 for adults. In Wijchen, these were, respectively, 22 and 13 interventions, and in Maasdriel, 24 interventions were found for youth. Most interventions addressed healthy eating and/or physical activity, a few paid attention to psychological or pedagogical aspects. Most participants were satisfied with the intervention(s) they used. For the question 'what does not work?', 61% of the answers were related to characteristics of the organization or social and political context of the intervention. Merely, all sectors expressed difficulties in involving parents. CONCLUSIONS: Many different interventions are applied in everyday practice within each city, but in a fragmented way. Too little attention is being paid to pedagogical aspects and to involving parents in preventing overweight.

Temperature-induced sperm nuclear vacuolisation is dependent on sperm preparation.

The influence of temperature during incubation on the degree of sperm nuclear vacuolisation was assessed by two different experiments. In a first experiment, motile spermatozoa from 24 patients were prepared by the swim-up technique and incubated either at room temperature or at 37 °C for up to 4 h. The presence of sperm nuclear vacuoles was determined by contrast-enhanced high magnification microscopy. No statistically significant difference was found in the degree of sperm nuclear vacuoles in both groups (RT: 45.6 ± 17.6%; 37 °C: 48.4 ± 17.0%) following 4 h of incubation. In a second experiment, spermatozoa from six patients were either prepared by swim-up or washed and incubated at 37 °C. After 4 h of incubation, a significant increase in sperm nuclear vacuolisation was found in washed sperm (from 51.5 ± 15.4% to 68.6 ± 9.0%; P < 0.05) but not in swim-up sperm (from 51.5 ± 15.4% to 48.2 ± 17.1%; n.s.). Our data show that the mode of sperm preparation does influence sperm nuclear vacuolisation at 37 °C (Experiment II). However, sperm nuclear vacuolisation is unaffected by temperature in motile sperm after preparation and isolation by swim-up.

Prediction of macrosomia at birth in type-1 and 2 diabetic pregnancies with biomarkers of early placentation.

OBJECTIVE: To evaluate the value of first trimester placental biomarkers (fß-hCG, PAPP-A, ADAM12, PP13 and PlGF) and fetal nuchal translucency (NT) in the prediction of macrosomia at birth in pregestational type-1 and type-2 diabetes (PGDM). DESIGN: Nested case-control study. SETTING: Routine first-trimester combined test. POPULATION: A total of 178 PGDM and 186 control pregnancies. METHODS: ADAM12, PP13 and PlGF concentrations were measured in stored first-trimester serum, previously tested for fß-hCG and PAPP-A. All concentrations were expressed as multiples of the median (MoM). Where applicable, the median MoMs of PGDM and control pregnancies were compared in relation to birthweight centiles (≤90th centile, non-macrosomic, versus >90th centile, macrosomic). Model-predicted detection rates for fixed false-positive rates were obtained for statistically significant markers, separately and in combination. MAIN OUTCOME MEASURES: Prediction of macrosomia in diabetic pregnancies. RESULTS: In the PGDM group, median ADAM12 MoM (0.88; P = 0.007) was lower than in the controls. Subgroup analyses showed that median MoMs of PAPP-A (0.65), ADAM12 (0.85), PP13 (0.81) and PlGF (0.91) were only reduced in the PGDM non-macrosomic birthweight subgroup (n = 93) compared with other weight subgroups. In the PGDM macrosomic birthweight subgroup (n = 69), MoMs of all markers were comparable with the control birthweight subgroups. The screening performance for macrosomia at birth in the PGDM group provided a detection rate of 30% for a 5% false-positive rate (FPR) and 43% for a 10% FPR. CONCLUSIONS: Macrosomia at birth in PGDM pregnancies may be predicted by normal levels of PAPP-A, ADAM12, PP13 and PlGF already in the first trimester of pregnancy. Fetal birthweight in PGDM offspring is partially determined by placental development during the first trimester of pregnancy. The present increase in fetal macrosomia may be related to better early glycemic control and placentation.

Modeling Down syndrome screening performance using first-trimester serum markers.

OBJECTIVE: To evaluate the modeled predictive value of three current screening markers (pregnancy-associated plasma protein-A (PAPP-A), free ß-human chorionic gonadotropin (free ß-hCG), and nuchal translucency (NT)) and four potential screening markers (a disintegrin and metalloprotease 12 (ADAM12), total hCG, placental protein 13 (PP13), and placental growth factor (PlGF)) for Down syndrome using different screening strategies. METHODS: All markers were measured in stored first-trimester serum of 151 Down syndrome cases and 847 controls. All marker levels were expressed as gestational age-specific multiples of the median (MoMs) and comparisons were made using the Mann-Whitney U-test. Detection rates (DRs) for fixed false-positive rates (FPRs) were modeled using different screening strategies. RESULTS: Significantly different median MoMs for Down syndrome cases compared to controls were found for PAPP-A (0.49 vs. 1.00; P < 0.0001), free ß-hCG (1.70 vs. 1.01; P < 0.0001), ADAM12 (0.89 vs. 1.00; P < 0.0001), total hCG (1.28 vs. 1.00; P < 0.0001), PlGF (0.80 vs. 1.00; P < 0.0001) and NT (1.74 vs. 1.01; P < 0.0001). The lower PP13 MoM in Down syndrome cases (0.91 vs. 1.00) was not statistically significant (P = 0.061). Adding the four new markers to the current screening strategy (i.e. first-trimester combined test) led to an increase in DR from 77% to 80% at a 5% FPR. The modeled application of a two-sample screening strategy (with some markers assessed early and others later in the first trimester) increased the DR to 89%. In a two-step contingent screening model, using an intermediate risk range of 1 in 100 to 1 in 2000 at biochemical screening (using all markers), the overall DR was 77%, but it was predicted that only 33% of women would require referral for NT measurement. CONCLUSIONS: First-trimester Down syndrome screening may be improved by adding new markers to the current screening test and by applying different screening strategies. The application of a two-sample screening model resulted in the highest predicted DR, but this should be confirmed in population-based prospective studies.

Longitudinal trends in fetoplacental biochemical markers, uterine artery pulsatility index and maternal blood pressure during the first trimester of pregnancy.

OBJECTIVE: To assess trends in levels of biochemical markers, uterine artery (UtA) pulsatility index (PI) and maternal blood pressure changes over time and study their relationships in uncomplicated first-trimester pregnancies. METHODS: The study population comprised 86 women with singleton pregnancies. In each woman, a blood sample was collected at 6-7, 8-9, 10-11 and 12-13 weeks' gestation. At the same visit blood pressure was measured and ultrasound examination was performed to measure the crown-rump length and Doppler flow velocity waveform patterns of both UtAs. Serum concentrations of pregnancy-associated plasma protein-A (PAPP-A), free ß-human chorionic gonadotropin (ß-hCG), A disintegrin and metalloprotease domain-containing protein-12 (ADAM-12), placental protein-13 (PP-13) and placental growth factor (PlGF) levels were measured in thawed specimens using an automated time-resolved fluorescence assay. Summary curves were created to describe normal ranges and trends over time. The data were analyzed with a linear mixed model with the log-transformed marker values as dependent variables. This allowed for flexible modeling of patterns over time. RESULTS: Sixty-eight pregnancies had an uneventful outcome, with the birth of an appropriate-for-gestational-age (AGA) infant. In these pregnancies serum PAPP-A, ADAM-12, PP-13 and PlGF levels increased with gestational age. The UtA-PI decreased and the mean arterial blood pressure remained constant. There were no significant correlations between maternal age, birth-weight percentile, gender and blood pressure and any of the biochemical markers. The serum markers were highly correlated with each other except for ß-hCG. A negative correlation was found between most biomarkers and UtA-PI, especially from 10 weeks onwards. Serum concentrations of ADAM-12 and PP-13 were lower in a small-for-gestational-age (SGA) subgroup born at term (n = 6), the former statistically significantly (P = 0.031), the latter non-significantly (P = 0.054), whereas UtA-PI was significantly higher (P = 0.02). Biomarker concentrations in 12 women delivering a large-for-gestational age infant did not differ from those delivering AGA neonates. CONCLUSION: There is a relationship between biochemical markers of early placentation and downstream resistance to flow in the UtAs in low-risk uncomplicated pregnancies, indicating differences in placentation. In a small series of SGA infants born at term we could demonstrate differences as compared to normal pregnancies, with potential value for screening.